Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) IV: Prognosis for End-Stage Renal Disease and Biomarker Validation

项目摘要 多囊肾病放射成像研究联盟（CRISP）是一个独特的，纵向的， 在241例常染色体显性遗传性多囊肾病（ADPKD）患者中进行的观察性队列研究， 2000年该联盟由亚拉巴马大学、芝加哥大学、埃默里大学的研究人员组成 大学、堪萨斯大学医学中心、马约诊所和匹兹堡大学。宽，长- CRISP的长期目标是确定疾病的自然史并发现预后生物标志物 可以准确预测长期肾脏预后。CRISP IV的目标是继续 CRISP队列随访5年以上，以完善CKD进展模型并加强 htTKV与肾脏结局之间的相关性，以使用现有和额外的 HALT PKD研究的随访数据，并将强大的新兴成像，遗传和 生物化学生物标志物，以提高个体患者的诊断准确性。为了实现这一目标， 具体目标是：目标1。继续对CRISP和HALT参与者进行随访。所有CRISP参与者， 未达到ESRD的受试者，以及在CRISP研究中心随访的HALT研究A受试者，将随访 年度血清肌酐测量。目标二。开发改进的模型来预测GFR轨迹， 进展为ESRD。现有的逻辑回归和轨迹模型将得到完善， 例如使用CRISP数据进行模型拟合开发的人工神经网络和分类树模型 和HALT-A数据进行外部验证。目标3：开发新的成像，生物化学和遗传生物标志物， 疾病进展。非常有前途的新生物标志物，正在从辅助研究中出现或正在 在CRISP中心正在进行的平行研究中开发的，将评估其改善 预测模型的准确性。

Project Summary The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) is a unique, longitudinal, observational cohort study of 241 autosomal dominant polycystic kidney disease (ADPKD) patients that began in 2000. The consortium consists of researchers at University of Alabama, University of Chicago, Emory University, University of Kansas Medical Center, Mayo Clinic, and University of Pittsburgh. The broad, long- term objectives of CRISP are to define the natural history of the disease and to discover prognostic biomarkers in early disease that can accurately predict long-term renal outcomes. The goals of CRISP IV are to continue follow-up of the CRISP cohort for 5 more years so as to refine models of CKD progression and strengthen the association between htTKV and renal outcomes, to validate disease models using existing and additional follow-up data from the HALT PKD study, and to incorporate powerful emerging imaging, genetic and biochemical biomarkers to improve the accuracy of prognostication for individual patients. To achieve this, the specific aims are: Aim 1. Continue follow-up of CRISP and HALT participants. All CRISP participants that have not reached ESRD, together with HALT Study A participants followed at CRISP sites, will be followed up with annual serum creatinine measurements. Aim 2. Develop improved models to predict GFR trajectories and progression to ESRD. Existing logistic regression and trajectory models will be refined and new approaches such as artificial neural network and classification tree models developed, using CRISP data for model fitting and HALT-A data for external validation. Aim 3. Develop novel imaging, biochemical and genetic biomarkers of disease progression. Highly promising new biomarkers that are emerging from ancillary studies or being developed in parallel ongoing studies at the CRISP centers, will be evaluated for their ability to improve the accuracy of prognostic models.